Methods for mapping tissue with optical coherence tomography data

ABSTRACT

Various methods are disclosed for mapping optical coherence tomography (OCT) data to facilitate review and diagnosis. In one aspect, high resolution 2D line scans are obtained along with lower density 3D cube scans and displayed in a manner to provide context to the clinician. In another aspect, OCT data is analyzed to provide information about non-uniformities of the tissue. Binary image maps of maps useful for determining tautness of membranes are also disclosed.

PRIORITY INFORMATION

This divisional application claims priority to U.S. patent applicationSer. No. 12/822,054, filed Jun. 23, 2010, which in turn claims priorityto divisional application U.S. patent application Ser. No. 11/717,263,filed Mar. 13, 2007, which application in turn claims priority to: U.S.Provisional Application No. 60/782,840, filed Mar. 16, 2006; U.S.Provisional Application No. 60/795,911, filed Apr. 28, 2006; U.S.Provisional Application No. 60/815,107, filed Jun. 20, 2006; U.S.Provisional Application No. 60/854,872, filed Oct. 27, 2006, and U.S.Provisional Application No. 60/857,451, filed Nov. 7, 2006, all of whichare incorporated by reference.

TECHNICAL FIELD

The present invention relates generally to methods for optical imagingof biological samples and for processing such images. In particular, theinvention is in the field of three-dimensional imaging using OpticalCoherence Tomography (OCT). Maps of elevation may be embodied asthree-dimensional surface renderings of elevation, topographical maps,or as color or grayscale maps.

BACKGROUND

Optical Coherence Tomography (OCT) is a technique for performing highresolution cross-sectional imaging that can provide images of tissuestructure on the micron scale in situ and in real time [Huang, D., E. A.Swanson, et al. Science 254 (5035): 1178-81]. OCT is a method ofinterferometry that determines the scattering profile of a sample alongthe OCT beam. Each scattering profile is called an axial scan, orA-scan. Cross-sectional images, and by extension 3D volumes, are builtup from many A-scans, with the OCT beam moved to a set of transverselocations on the sample. Motion of the sample with respect to the OCTscanner will cause the actual locations measured on the sample to bearranged differently than the scan pattern in scanner coordinates,unless the motion is detected and the OCT beam placement corrected totrack the motion.

In recent years, frequency domain OCT techniques have been applied toliving samples [Nassif, N. A., B. Cense, et al. Optics Express 12(3):367-376]. The frequency domain techniques have significant advantages inspeed and signal-to-noise ratio as compared to time domain OCT [Leitgeb,R. A., et al. Optics Express 11(8): 889-894; de Boer, J. F. et al.Optics Letters 28: 2067-2069; Choma, M. A. and M. V. Sarunic OpticsExpress 11: 2183-2189]. The greater speed of modern OCT systems allowsthe acquisition of larger data sets, including 3D volume images of humantissue.

In the case of ophthalmology, a typical patient can comfortably hold hiseye open for a few seconds. OCT systems can advantageously use these fewseconds to collect extensive images [Hitzenberger, C. K. et al.“Three-dimensional imaging of the human retina by high-speed opticalcoherence tomography.” Optics Express 11(21): 2753-2761, and “SpectralRadar: Optical Coherence Tomography in the Fourier Domain”, Lindner, M.W., Andretzky, P., Kiesewetter, F., and Hausler, G. in B. E. Bouma andG. J. Tearney, Handbook of optical coherence tomography (Marcel Dekker,New York, 2002)].

Various approaches have been developed for analyzing and the displayinginformation obtained from OCT methods. For example, in U.S. patentapplication Ser. No. 11/223,549, filed Sep. 9, 2005 (and incorporatedherein by reference), a method is disclosed for generating elevationmaps or images of a tissue layer/boundary with respect to the locationof a fitted reference surface, comprising the steps of finding andsegmenting a desired tissue layer/boundary; fitting a smooth referencesurface to the segmented tissue layer/boundary; calculating elevationsof the same or other tissue layer/boundary relative to the fittedreference surface; and generating maps of elevation relative to thefitted surface.

The subject application relates to additional display methods which willfacilitate the diagnosis and treatment of pathologies in the eye of apatient.

SUMMARY OF THE INVENTION

In one aspect of the subject invention, the OCT device is arranged toobtain both high resolution two dimensional scans (slices) as well aslower resolution three dimensional data cubes. In a preferredembodiment, information from both types of scans is displayed so thatthe lower resolution three dimensional scan can provide context orlocation cues for the higher resolution scans.

In another aspect of the subject invention, image data from a firstmeasurement can be displayed in conjunction with image data from asecond, later measurement to help align the patient with the device.This aspect can be particularly useful when the two measurements aretaken during different visits to the clinician.

In another aspect of the subject invention, the system is configured tocontrol the orientation of displayed images. The orientation can beselected using various criteria such as providing a consistent view orto better display features within the image.

In another aspect of the subject invention, maps are generated whichshow non-uniformities of features within the sample such as the eye.Such an approach can be useful to show textural features which can becorrelated to various disease states such as the presence of drusen orexudates.

In another aspect of the subject invention, maps can be generated whichcan illustrate the connections between membranes and tissue layers suchas the retina. Such maps can be useful to determine characteristics suchas the disruption or curvature of tissue layers or tautness of themembranes.

In another aspect of the subject invention, image and/or map informationis compared to a threshold with the results then being displayed as abinary map.

Further objects and advantages of the subject invention will becomeapparent from the following detailed discussion taken in conjunctionwith the drawings in which:

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a display screen of an OCT system showing three windows andillustrating two high resolution scans and one lower resolution scan.

FIG. 2 is a display screen similar to FIG. 1 wherein the two highresolution scans are replaced by reverse video images.

FIG. 3 is a display screen of an OCT system illustrating both highresolution scans, a lower resolution scan and a issue thickness overlay.

FIG. 4 is a display showing two high resolution scans in conjunctionwith displays of tissue surfaces extracted from the lower resolutionscans.

FIG. 5 is a display showing an en face image on the left hand sidecoupled with a high resolution compound circle scan on the right handside.

FIGS. 6 a through 6 d shows how an ophthalmoscope fundus image can beoverlaid by an image derived from an OCT data scan acquired during aprevious visit. The image overlay can be used to facilitate patientalignment.

FIG. 7 is a 3D volumetric rendering of OCT image data.

FIGS. 8 a and 8 b are layer maps shown in different spatialorientations.

FIG. 9 is an en face color map of RPE elevation in microns relative to asurface fitted to the RPE.

FIG. 10 is an en face map showing root-mean-squared deviation of the RPEdepth about the local mean depth.

FIG. 11 is a B-scan showing the detection of small voids larger than thenormal dark spots that are due to speckle.

FIG. 12 is an en face map showing the density of voids in the retina.

FIG. 13 is a B-scan showing the presence of fluid both below and abovethe RPE.

FIG. 14 is an en face map showing the depth of fluid in microns betweenthe RPE and a parabolic surface fitted to the RPE.

FIG. 15 is an en face map showing the depth of fluid in microns in thevicinity just above the RPE.

FIG. 16 is an en face view indicating points of membrane attachment.

FIG. 17 is an en face map showing points where membranes approach thevitreo-retinal interface (VRI) and the curvature of the VRI at thatpoint.

FIG. 18 is a horizontal B-scan through a point of high membranetraction.

FIG. 19 is a diagonal B-scan composed of lines extracted from a set ofparallel horizontal B-scans.

FIG. 20 is a flow chart illustrating a sequence of steps to generate abinary map.

FIG. 21 are images including a color coded elevational map of the RPE aswell as two binary images.

FIG. 22 are images including a color coded elevational map of the RPE aswell as two binary images.

FIG. 23 is a diagram of an OCT system which can be used to implement thesubject invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The approaches discussed herein are preferably implemented on a devicefor measuring samples using optical coherence tomography (OCT). One suchdevice has been marketed for some time by the assignee herein under thetrademark Stratus OCT. The assignee just recently introduced a newsystem under the trademark Cirrus HD-OCT. This device is a compositesystem which includes not only an OCT scanner but also an ophthalmoscopewhich is aligned with the OCT system along a common optical axis. Adescription of a system having both an OCT module and an ophthalmoscopeis set forth in U.S. Patent Publication No. 2006/0228011, incorporatedherein by reference.

The Cirrus device is a frequency domain OCT system with a broadbandlight source and a spectrometer. A preferred spectrometer system isdescribed in U.S. Patent Publication No. 2007/0030483, which isincorporated herein by reference.

It is believed that the concepts discussed and claimed herein areindependent of the specific hardware used to take the measurements andcan be understood by one skilled in the art by reference to the variouspatents and publications cited above and listed below which are allincorporated herein by reference and include:

-   -   U.S. Patent Publication No. 2005/0254009    -   U.S. Patent Publication No. 2006/0164653    -   U.S. Patent Publication No. 2006/0164639

Although not required for an understanding of the inventions claimedherein, additional details of the assignee's Cirrus system are set forthin three provisional applications; U.S. Provisional Application No.60/815,107, filed Jun. 20, 2, U.S. Provisional Application No.60/854,872 filed Oct. 27, 2006, and U.S. Provisional Application No.60/857,451, filed Nov. 7, 2006, which are incorporated herein byreference.

Collection of Compound OCT Scans

The first embodiment of the subject invention relates to a method ofacquiring OCT data sets to provide both high definition scan(s) and alower resolution data cube within a short period of time so that thedata cube provides context for the high definition scan(s).

Clinicians want to know where retinal OCT tomograms lie in relation tolandmarks on the retina. In cases of retinal pathology, clinicians wantto see a cross-section of the pathology in the context of a map of theretina. One example of this is a cross-section of retinal edemapresented in the context of a retinal thickness map. In a preferredembodiment, two sequential scans of differing types (resolutions) areperformed and simultaneously displayed, preferably on the same display.It is particularly advantageous when these two display types can beacquired using a single interaction with the user interface, say asingle click or a single voice command.

In StratusOCT (Paunescu, L. A., J. S. Schuman, et al. “Reproducibilityof nerve fiber thickness, macular thickness, and optic nerve headmeasurements using StratusOCT.” Invest Ophthalmol Vis Sci 45(6):1716-24) a nearly-simultaneous fundus image is captured with the OCT,showing the location of the OCT beam on the retina. Motion of the eyebetween the fundus image and OCT scan can affect the quality ofcorrespondence. Simultaneity here simply means that data collectionhappens quickly enough that the side-by-side display of the two types ofdata are sufficiently synchronized that they present two views of thesame object and structure.

Publications by Podoleanu (U.S. Patent Publication No. 2003/0199769),for example, suggest taking a Scanning Laser Ophthalmoscope (SLO) imagepoint-by-point simultaneously with the OCT scan. This approach uses anadditional imaging system consisting of a beam splitter and the SLOdetector, and depends on hardware alignment between the OCT and SLOdetectors.

For the purpose of providing a fast fundus image, a Line Scanning LaserOphthalmoscope (LSLO) is generally faster than the SLO and equallyuseful, as is the line-scan ophthalmoscope (LSO) of U.S. PatentPublication No. 2006/0228011.

In a preferred embodiment, high quality (resolution) tomograms areprovided in conjunction with an OCT data cube that provides context forthem. The OCT data cube is registered with the high resolution scans byvirtue of being acquired with the same optics. The data cube can providea fundus image, retinal thickness maps, or other reductions of thevolume data, to provide context for the high quality tomograms.

An OCT data cube provides context for any tomogram extracted from thecube. One would like to have high definition tomograms, with transversespacing of A-scans comparable to the width of the probe beam (thetransverse optical resolution). However, time and data storageconstraints make it difficult to collect sufficiently many A-scanswithin the cube for every tomogram to have such high definition.

Often the clinician will concentrate only on one or two tomograms withinthe volume. It is efficient then to spend time and storage space on afew high definition tomograms, covering the remainder of the volume withrelatively coarsely-spaced A-scans.

In application to imaging the retina, a cube covering the area of retinacorresponding to 20° visual field is covered with a square array ofA-scans. Preferably between 100×100 and 500×500 A-scans cover thevolume, though the number may be either greater or smaller. The A-scansin the cube may be spaced between 0.2° and 0.04°, while the 1/e²diameter of the OCT beam at the retina corresponds to 0.05°, so thereare gaps between the tissue sections sampled by adjacent A-scans. Inaddition to the cube, we acquire two B-scans consisting of higherdensity A-scans than used to scan the volume, covering 20°. The highdensity A-scans are preferably spaced between 2 and 20 times closertogether than the lower density A-scans used to cover the cube. SpacingA-scans more closely continues to give benefits, even when the spacingbetween A-scans is about half the beam diameter. In a preferredembodiment, at least 500 and more preferably at least 1000 A-scans areused to generate each B-scan.

The results of one such composite scan are shown in FIG. 1. FIG. 1includes an en face view in the upper left quadrant and two highresolution tomograms, one in the upper right and the other in the lowerleft quadrants. The en face view comes from integration of the OCT dataalong the beam direction, giving an image similar to that of a scanningophthalmoscope. In FIG. 1, we see the en face view with two tomogramstaken from the same volume. The displays in the upper left and lowerright quadrants are high density/resolution B scans. The red horizontaland yellow vertical lines in the en face image show the clinician thelocation of the high resolution B scans. The icon in the upper leftcorner of the high resolution B scans contains a color coded componentto associate it with the location identified in the en face view.

In FIG. 2, the high density/resolution B scans have been replaced bytheir reverse video images. The gray scale is inverted in the tomograms,with black representing more light scattered from tissue, to better showthe detail. Depending on the design and performance of the OCT system, athird cut of the volume, with constant depth, may also be attainable inhigh definition.

FIG. 3 shows tissue thickness maps derived from a 3D block of OCT data,with the high definition tomograms plotted to the right. (The black andwhite image of the retina, over which the thickness map is overlaid, isfrom a scanning ophthalmoscope.)

FIG. 4 shows images of two high definition scans presented with surfacesextracted from the 3D block of OCT data. Indicia are provided on each ofthe views to help provide context. For example, the bottom left handhigh definition image includes a small square in the upper left cornerwith a green bar. The location of the green bar within the squaregenerally shows the location of the slice within the cube. Moreover,this indicator (green bar within a square) is overlaid on the lowerdensity en face image. Here the green bar directly shows the clinicianwhere within the larger cube the slice has been taken. The bottom righthand high definition image is similarly identified with a blue bar inboth the high definition image and on the en face image.

While the description here describes a lower density cube and a smallnumber of higher density planes, it is generally understood that oneversed in the art can see the application of general volumes collectedwith lower density scans and a small number of higher density surfaces.For example, one or more high resolution circle scans are acquired, withcompanion lower density cube scan. A circle scan is particularly usefulfor evaluating the health of the retina by use of retinal layerthickness measurements. Multiple neighboring high resolution circlescans are useful for improving thickness measurements, for example byaveraging thickness measurements or improving boundary detection. FIG. 5is a display of an en face image on the left hand side coupled with ahigh resolution compound circle scan on the right hand side.

The high definition B-scans in the example of FIG. 1 were acquiredbefore the cube, but they may also be acquired after the cube or in themiddle of acquiring the data cube. The composite scans are acquired inconjunction with the motion-correction method described in U.S. PatentPublication 2006/0164653 cited above. Briefly, a sparse set of A-scansis taken before or after the composite scan, so that the high definitionscan and the cube can both be corrected for patient motion. When one ormore high definition B-scan is acquired first, especially when at leastone such scan is taken along the slow-scan direction of the volume,it/they may be used to help in motion correction, even though this isnot their primary purpose. When used in this manner, it is advantageousto collect the high density scans first. The composite scans can also beacquired in conjunction with tracking by the LSLO as described in U.S.Patent Publication No. 2006/0228011, cited above, so that transversemotion of the eye is corrected during data acquisition.

Alternatively, a high resolution cube scan can be acquired, constrainedwithin a volume imaged by a lower density cube scan. A high resolutionvolume scan can even be acquired which contains the lower density volumescan. When the high resolution volume scan covers a small volume, forexample of the macula or the optic nerve head, in some cases it can beacquired so quickly that the probability of motion over the acquisitiontime is low. However, acquisition of large high density volumes canrequire sufficient time for acquisition that motion occurs. In thiscase, the lower density volume can be used to correct for motion in thehigh resolution volume. The lower density volume may itself have beencorrected for motion using a sparse set of A-scans.

The high definition scans provide a good starting point for imagesegmentation. Some factors that help in segmentation are theover-sampling of the speckle in the high definition image, and thehigher sensitivity coming from reduced motion artifact. Severaltechniques exist for extending a segmented tomogram to neighboringtomograms, so segmentation of the entire cube can be improved by thepresence of the high definition scans.

Presentation of the high definition scans in context of the cube can nowbe performed in a number of effective ways. Straightforward volumerendering, in which the high definition scans naturally stand out, showsthe high definition scans in 3-dimensional context. Also effective is aplot of the high definition scans in perspective, over a base mapconsisting of an en face projection, macular thickness, or any other mapfrom the 3D scan.

The data resulting from the volume acquisition in such a composite scancan be significantly reduced in size, but reduced in ways that keepimportant information to provide context for the high definition scans.The data cube can be reduced to an en face image, and/or a retinalthickness map, and/or an RNFL map, for example.

The presentation can be reduced in size as well, showing OCT-generateden face images, macular thickness or other maps, and high definitiontomograms all on one sheet, screen, or report.

In its broad form, the concept includes operating the scanner of an OCTdevice to obtain a first set of high resolution measurements at aplurality of locations along a first line in the X-Y plane. The scannerof the OCT is also arranged to collect a data cube based on a second setof lower resolution measurements at a plurality of locations across theX-Y plane. The average spacing between the locations for the data cubeis larger than the average spacing for the high resolution measurements.In a preferred embodiment, the average distance between adjacentlocations for the high resolution measurements is less than twenty fivepercent (and more preferably less than ten percent) of the averagedistance between locations in the lower resolution measurements. Theseresults can be stored in memory and displayed as shown in FIGS. 1 to 5.

In a preferred embodiment, wherein the high resolution measurement scansare taken first, it is desirable that the second set of lower resolutionmeasurements be initiated less than four seconds after the highresolution measurements had been initiated. Ideally, the lowerresolution scan automatically starts following the high resolution scan.

The high resolution measurements are preferably along a line. The linecould be curved or straight. In a preferred embodiment, two highresolution line scans are performed, perpendicular to each other. Theresults of such a measurements are shown in the top two quadrants ofFIG. 1.

Repeat Scans

The previous section described a thickness map derived from the 3D OCTdata blocks overlaid on ophthalmoscope images (FIG. 3). The en face viewfrom integrated intensity maps is valuable in later visits to repeat OCTdata collection from the same tissue. The operator sees a liveophthalmoscope fundus image from the ophthalmoscope with an overlay of ascan pattern and a semi-transparent version of the en face image fromthe previous OCT data cube. FIG. 6 a is an ophthalmoscope fundus imageand FIG. 6 b is an en face OCT intensity map. FIG. 6 c shows the en faceOCT image overlaid on the ophthalmoscope fundus image.

The operator manually registers these two images by adjusting a fixationtarget position and/or moving the scan location. FIG. 6 d shows theoverlay correctly adjusted. Optionally, if sufficient computationalresources are available, the image can be overlaid and adjustments tothe fixation target position may be made automatically.

In the illustrated embodiment, the overlay is an en face integratedimage derived from OCT data and the underlying image is from theophthalmoscope. Those skilled in the art will understand that othervariations are possible. For example, the en face image can be displayedwith an overlay of a portion of the ophthalmoscope image. Alternatively,alignment can be achieved by comparing a stored ophthalmoscope imageoverlaid with a current ophthalmoscope image. Similarly, alignment canbe achieved by comparing a stored OCT image (en face or other image)overlaid with a current OCT image. In all cases, the alignment of thesystem is adjusted so that the currently obtained image matches apreviously obtained image. The previously obtained image could have beenderived from an earlier visit by the patient.

Alignment can be obtained by moving the patient's eye, and hence thelive underlying image, or by moving the optical imaging alignment, andhence moving the overlaid image since it is aligned with the opticalaxis. In practice, when the fixation target has limited locations, onlyrough alignment is achieved through eye motion and the fine adjustmentof the alignment is achieved by optical alignment of the galvos.

Various ways can be used to improve the usability of the overlay. Theoverlay can be semi-transparent or patterned. The overlay can have acheckerboard pattern or a striped pattern, where a portion (say half ofthe squares or stripes) of the pattern is totally transparent. Variouscolors can be used to enhance the user's ability to see alignment. Onesuch color scheme converts the grayscale ophthalmoscope image to shadesof red while changing the grayscale of the overlay. When bright regionsalign, the red and green add to make a new color, like yellow.Similarly, when dark regions align they create a darker region because,when they were misaligned, the misaligned color creeps into andbrightens the region.

Standardization of Orientation

OCT images of the back of the eye are typically acquired by sendinglight in and out through the human pupil. The orientation of the data inthe resulting OCT data cubes changes slightly with the position of theOCT beam in the pupil. In order to properly compare measurements betweenvisits, the orientation of the data should be standardized. Thisstandardization of orientation can be achieved by identifying ananatomical layer such as the retinal pigment epithelium and rotating theOCT data blocks, either to a standard orientation of that layer, or tomatch the orientation of that layer. Methods to find a reliable surfaceand present OCT data relative to that surface are described inco-pending U.S. patent application Ser. No. 11/223,549, cited above.

Another standardization of orientation can be achieved by orientingsegmented surfaces in a standard orientation for display. It isadvantageous that the view is standardized to enable visit-to-visitcorrespondence between the displays. The view of the ILM (inner limitingmembrane) is preferably oriented to show peaks and valleys of thesurface. This orientation should match the orientation of the combinedRPE/mM map.

Examples of this concept are illustrated in FIGS. 7 and 8. The denselysampled volumetric data collected by the OCT scanner can be displayed asa 3D volumetric rendering (FIG. 7) or represented more abstractly aslayer maps (FIGS. 8 a and 8 b). The orientation of the tissue (retina)can vary from one scan to the next in relation to optical axis and thusthe cube of data (FIG. 8). As a result of this variability inorientation, the clinician does not always have the same view of thetissue from one patient visit to the next. As noted above, it would bevery beneficial to the clinician if he/she were able to see the 3Drepresentation of the tissue in the same orientation regardless of thevariation in the imaging axis. To optimize/normalize the viewing angle,an algorithm can estimate the orientation of the tissue in respect tothe data coordinate system (cube of data) and automatically rotate the3D image such that the tissue would always appear in the sameorientation (in respect to the “rendering” coordinate system). By doingso, the doctor will see the tissue in the same orientation and thereforewill be more effective in comparing the tissue/pathology from one visitto the next. Without an automated algorithm the operator will have tospend tens of seconds to orient each scan and will likely result ininconsistencies from one operator to the next.

In is broad form, the subject method requires analyzing the OCT data todetermine the orientation of the image. Thereafter, the image is rotatedto a preferred orientation and this resulting image is displayed. Theimage can be rotated to best view a particular structure, to match aprevious view derived from data obtained at an earlier time or tomaximize viewing of features of interest.

Diagnostic Metrics of Texture and Heterogeneity

Various pathologies of the eye can cause non-uniformities which can beimaged and or analyzed. This aspect of the subject invention relates toidentifying such non-uniformities and generating images of thenon-uniformities. Alternatively, once the non-uniformities areidentified, they are quantified in a manner to aid in the diagnosis of adisease state.

One example of a non-uniformity in the eye are drusen. Drusen are smallmounds of amorphous material deposited within Bruch's membrane by cellsin the retinal pigment epithelium (RPE) in cases of age-related maculardegeneration. The presence of many drusen of diameter greater than 100microns can be a predictor of retinal atrophy or choroidalneovascularization. In an OCT scan, drusen appear as mildly reflectiveregions causing shallow elevations in the RPE. By using avolume-scanning OCT system, these regions may be identified andindicated in an en face view of the scanned region. After the detectionof drusen larger than 100 microns, a map can be generated indicating thelocations of such large drusen in an en face fundus view. Either theextent or just the center of such drusen could be indicated in the map.

Without needing to detect individual drusen, a map of the roughness ofthe RPE could indicate the presence and general location of drusen.Roughness may be defined as the root-mean-squared vertical deviation ofthe RPE boundary about a local mean or a surface fitted to an RPEsegmentation. Other equivalent metrics of deviation in elevation orcomplexity of the surface texture may also be used. Roughness could alsobe defined in terms of variation in brightness along the RPE or asmoothed or fitted version of the RPE. Such a map of roughness couldalso be constructed for the vitreo-retinal interface as an indicator ofglaucoma.

For diabetic macular edema, the presence of hard exudates is indicativeof the resorption of serous fluid from leaking capillaries. Theselesions will appear in an OCT scan as small bright spots above the RPEthat may be detected by thresholding and possibly by the presence ofshadows. The presence of hard exudates in the fovea will impair centralvision, so a map of these heterogeneities marked with the location ofthe fovea could be useful in explaining vision deficits.

Maps of other characteristic parameters of heterogeneity such as thedensity or average size of drusen or exudates could also prove to haveclinical utility. For example, estimates of drusen volumes can beachieved by computing the volume bounded by the RPE and a smoothedsurface RPE fit, constrained within the field of view. In fact, volumemeasurements can be achieved measuring the volume bounded by any twosegmented surfaces or the volume bounded by any two surfaces determinedfrom the volume data. Either surface may be acquired throughsegmentation, heuristically acquired, estimated by fitting any knownsurface to data, or any other means for stipulating a surface. Once thetwo surfaces are defined, measurements can be made either of the volumebetween the two surfaces or the surfaces can be subtracted and eitherpositive or negative volumes can be computed from the difference surfaceand any fixed plane, bounded within the field of view. Other measurescan be made on one of the surfaces by itself, such as the total area ofthe surface, area of the surface exceeding a specified height, or anymeasure of the variation of the surface. Still other measures can bemade as functions of the two surfaces, such as the variation of thesurface defined be the difference between the two surfaces or the areaof the domain of all points of the difference surface that exceed agiven height. Displays can be presented of these volumes, surfaces, orareas or values can be tabulated for volume or area or other valuesfunctionally dependent on these data.

Macular edema can manifest itself as a diffuse swelling or as theformation of cysts in the retina. The OCT image (or the undemodulatedimage data, which represents a linear combination of scattererresponses) may be analyzed to give tissue texture parameters that canindicate the degree of cyst formation. These parameters may includewidth or side lobe height of the autocorrelation function, statistics ofintensity, or a combination of these. Such a map of sponginess orporosity would help identify the presence of diffuse (or both cystic anddiffuse) fluid in tissue. The distribution of cyst sizes could beindicated with a metric such as such as average fluid-space diameter tocharacterize the diffuseness of the edema. Other measures, such as thevolume between two surfaces, statistics such as the mean distancebetween two surfaces or the standard deviation of the mean distancebetween two surfaces are measures of the size of the swelling. 3-Ddisplays of differences of two surfaces, 2-D displays of the height(encoded in color or grayscale) of a surface or maps of the distancefrom a point on a surface to another surface, or 2-D binary displays ofthe points meeting some criteria can be used to visualize measures ofthe edema. Equivalently, measures of volumes or areas satisfying somecriteria may be tabulated and displayed.

Metrics of texture could also be used to quantify the clarity of cysticspaces and/or vitreous humor. Clear dark fluid in these spaces indicatesthe absence of cells, which are an indicator of inflammation and/orinfection. If cells were present in these areas, one would expectincreased reflectivity characteristic of isolated scatterers, eventuallydeveloping into full speckle. The difference between background noise,isolated scatterers, and full speckle could be indicated by suchstatistical indicators as the ratio of the mean intensity to thestandard deviation of intensity, or the axial and lateralautocorrelation function widths and side lobe heights.

Although the above concepts have been described as two-dimensional enface maps of texture and heterogeneity metrics, the same notions couldbe applied to three-dimensional representations or three-dimensionalrenderings of surfaces containing these metrics as functions of the twolateral dimensions. Also, scalar summary metrics of these features, suchas average values and/or deviations of these metrics over the imagedvolume, may serve a similar purpose.

Drusen or hard exudates may be identified using a fundus camera, but theuse of OCT data has the potential for more reliable detection, given theadditional information in the depth axis. Due to the absence of depthinformation from fundus photography, a roughness analysis of the RPE orVRI, a porosity analysis for macular edema, or a textural identificationof cyst inflammation would simply not be possible.

In a preferred approach, the non-uniformities can be displayed withreference to a landmark within the eye. Here, the term landmark isintended to include features such as the fovea, vessels, lesions, thefundus image itself, fluid regions, anatomical features and pathologicalfeatures. A collection of landmarks can itself be a landmark. Includedin the definition of textures: roughness, clarity, reflectivity,connectedness and elevation.

Retinal Fluid Maps

Another type of non-uniformity of interest is associated with cysticregions of retinal fluid.

Although diffuse edema is a common characteristic of retinal disease,cystic regions of fluid can be located and delineated using analysis of3-D OCT scans. Intraretinal fluid usually occurs as cystic edema in theouter nuclear and outer plexiform layers. Subretinal fluid will poolinto clearly defined areas just above the RPE, while choroidal diseaseis characterized by prominent pockets of fluid below the RPE.

Three-dimensional raster scanning of the retina facilitates the creationof detailed 2-D maps of the retina analyzed by depth. Maps ofintraretinal, subretinal, and/or sub-RPE fluid can help diagnose theexistence and progress of exudative retinal disease.

Fluid can be detected by thresholding of the retinal images, followed bya removal of small regions below that threshold (to remove voids due tospeckle or shadows). Voids in the retina that do not approach the RPE(as detected by a separate segmentation process) would be classified asintraretinal, while pockets that border the RPE would be characterizedas subretinal. Sub-RPE fluid could be approximately defined by fitting asmooth surface such as a paraboloid to the RPE (see U.S. applicationSer. No. 11/223,549, cited above) and its discussion of referencing theelevation of the RPE to that surface fit. Pronounced pockets of fluidwould stand out from the fitted surface and appear as spots on anotherwise blank map. FIG. 9 is an en face map of RPE elevation inmicrons relative to a surface fitted to the RPE. Detachments of the RPEstand out in light regions.

FIG. 10 is an en face map showing root-mean-squared deviation of the RPEdepth about the local mean depth. The red and yellow patches in thesuperior half of the field represent small inhomogeneities, likelydrusen, while the white-and-yellow ring below indicates a large, smoothinhomogeneity, likely an RPE detachment. FIG. 11 is a B-scan showing thedetection of small voids larger than the normal dark spots that are dueto speckle. FIG. 12 is an en face map showing the density of voids inthe retina. Yellow indicates an elevated density while red indicates thehighest densities.

As with the textural maps, the fluid-pocket information could bepresented in a wide variety of formats. Two-dimensional en face maps orimages of texture and heterogeneity metrics could optionally be appliedto three-dimensional representations or three-dimensional renderings ofsurfaces containing these metrics as functions of the two lateraldimensions. Also, scalar summary metrics of these features, such asaverage values and/or deviations of these metrics over the imagedvolume, may serve a similar purpose.

FIG. 13 is a B-scan showing the presence of fluid both below and abovethe RPE, but below the neurosensory retina. FIG. 14 is an en face mapshowing the depth of fluid in microns between the RPE and a parabolicsurface fitted to the RPE. FIG. 15 is an en face map showing the depthof fluid in microns in the vicinity just above the RPE. Compared to themap of FIG. 14, one can see the subretinal fluid is clustered at the“shoulders” of the large RPE detachments indicated in the map of sub-RPEfluid.

Integrated Intensity

A primary concern of the OCT analysis of the retina is the integrity ofthe tissue following degenerative diseases. A map of the integral ofreflectivity above the RPE (perhaps normalized to RPE reflectivity oroverall intensity in the A-scan) may have value as an indicator ofprognosis after healing. Integrated intensity within the RPE itself maybe indicative of AMD, atrophic RPE, and Retinitis Pigmentosa. Belowthis, the integrated intensity in the choroid, taken as a percentage ofoverall integrated reflectivity, may similarly indicate RPE atrophy, RPEbleaching, retinal atrophy, etc. Images or maps of these parameterscould be viewed in a 2-D or 3-D format and possibly combined withrepresentations of other retinal parameters.

Just as intensity can be integrated above the RPE, it can be integratedeither above or below any surface, either detected in or determined fromthe data, or established a priori. Intensity can also be integratedbetween two surfaces, such as from the ILM to the RPE, or from the RPEto some fixed N pixels (or voxels) above (or below) the RPE.

Further information about integrated intensity maps can be found in U.S.Patent Publication No. 2006/0119858, incorporated herein by reference.

3D Analysis of Membrane Geometry to Identify Traction Forces

Posterior Hyaloid and epiretinal membranes can pull on the retina,causing its deterioration. Surgical removal of these membranes must bedone carefully so as not to further damage the retina during theremoval. Knowing the degree and direction of the tractional forces onthe retina would be useful for diagnosing whether membrane removal isindicated. If surgery is performed, such knowledge would help determinethe best points to detach and in what directions to apply traction whenremoving the membrane. Traction force could be estimated by looking atthe tautness of the membrane and other nearby points of attachment. Thisinformation could be displayed as overlays for en face images that showattachment points color-coded with estimated traction force (or aclinically relevant component of force, such as the component that isnormal to VRI, normal to RPE, or the total magnitude) or a metric oflocal surface curvature. One could also similarly color membranes incross-sectional B-scans using this information.

Another visualization would be to extract a cross-section perpendicularto the contour of the membrane attachment and identify the presence ofholes underneath points of attachment. From an en face view indicatingthe points of attachment, a user could scroll along the contour wherethe membrane attaches and view the stage of hole formation based on athorough exam of all attachment points. The stage assessment couldpossibly be automated as well, giving an en face view of the dataindicating the points of attachment with, e.g., green contours showingpoints of attachment with no hole formation, yellow showing attachmentswith a mild hole formation, and red showing attachments with underlyingholes of an extreme stage.

FIG. 16 is an en face view indicating points of membrane attachment.FIG. 17 is an en face map showing points where membranes approach thevitreo-retinal interface (VRI) and the curvature of the VRI at thatpoint. The dark green areas have no membrane detected near the retina,while the light green area shows membranes in proximity to the retinabut little or no evidence of pulling on the VRI. Yellow areas have somemembrane traction indicated by the VRI curvature, while the red areashave the sharpest peaking in the VRI, indicating strong traction. FIG.18 is a horizontal B-scan through a point of high membrane traction asindicated in red on the traction map. The orientation of the B-scancould be automatically selected according to the membrane and retinageometry. FIG. 19 is a Diagonal B-scan composed of lines extracted froma set of parallel horizontal B-scans. The direction of this B-scan isperpendicular to the ridge in the VRI, thus showing a higher angle ofmembrane attachment (even when larger line spacing is taken intoaccount).

In its broad form, this concept includes the steps of identifyingmembrane attachments to the retina from OCT image information anddisplaying a map illustrating the identified membranes. The displaycould illustrate tautness of the membranes or the disruption of layers.We can display suspect B-scans, allowing the operator to determine ifthere are actual holes. The maps can be displayed with respect to alarger field of view (the SLO). We can also reference the epiretinalmembrane (ERM). The distortion of the ERM can be correlated with retinallayer disruption.

Binary Maps

When attempting to differentiate healthy from diseased tissue, measuresare often thresholded. Various thresholds are often set depending onconfidence and/or reliability. FIG. 20 is a flowchart for how to converta surface, segmented from a 3-D volume and into a binary image. Areas ofconcern can be measured by simple pixel counts converted to area.Examples of such binary maps are provided in FIGS. 21 and 22

The left hand displays of FIG. 21 shows RPE elevation maps. The twodisplays on the lower right are two binary maps with different thresholdlevels. The area covered by the white pixels (where data exceeded thethreshold) is a measure of the likelihood of disease. FIG. 22 is similarto FIG. 21 but illustrates the situation where there are very fewregions of concern. The membrane attachment map shown of FIG. 8 can bebinarized where the threshold is chosen to measure membrane attachment.

In broad form, the method can include the steps of comparing OCT imagedata to a threshold and displaying a binary map of the data whereinpoints that exceed the threshold are displayed in one format and pointsthat are below the threshold are displayed in a second format. In apreferred embodiment as indicated by the flowchart of FIG. 20, anelevational map can be generated and distances from the map to anothertissue layer or boundary can be computed and compared to a threshold.This information can then be displayed in a binary map. The binary mapcan be displayed as an overlay on another image of the eye.

A simplified illustration showing the basic elements of an OCT system2310 are shown in FIG. 23. Further details about OCT systems can befound in the various articles and patent citations set forth above aswell as in U.S. Provisional Application No. 60/815,107, previouslyincorporated by reference.

OCT system 2310 includes a light source 2320 which can be a laser diode.A portion of the light is directed along a sample path to the eye 2330.The sample path includes a means 2340 for scanning the beam over the eyewhich can be a pair of galvanometer driven minors. Light returned fromthe eye is combined with light from the source in an interferometerarrangement 2350. The output of the interferometer is supplied to adetector which can be a spectrometer 2360. The output from thespectrometer is supplied to a processor 2370 which will include a memory2380 for storing the results. The results can also be shown on a display2390.

While the subject invention has been described with reference to thepreferred embodiments, various changes and modifications could be madetherein, by one skilled in the art, without varying from the scope andspirit of the subject invention as defined by the appended claims

1. A method of displaying information related to a membrane attached tothe retina of an eye based on image data acquired by an opticalcoherence tomography (OCT) system comprising the steps of: identifyingattachments of the membrane to the retina from the image information;and displaying an image illustrating the identified membraneattachments.
 2. A method as recited in claim 1, wherein said imageindicates the tautness of membrane.
 3. A method as recited in claim 2,wherein the level of tautness is indicated by color coding.
 4. A methodas recited in claim 1, wherein the image further indicates thedisruption of tissue layers within the eye.
 5. A method as recited inclaim 1, wherein the membrane is displayed as an overlay with respect toan en face image of the eye.
 6. A method as recited in claim 1, whereinsaid image further indicates holes associated with the membraneattachments.
 7. A method as recited in claim 1, wherein said imageincludes B-scans of one or more orientations through a selected point ofmembrane attachment.
 8. A method as recited in claim 7, wherein theorientation of the B-scan is automatically selected according to themembrane and retina geometry.
 9. A method as recited in claim 1 whereinthe membrane is an epiretinal membrane.
 10. A method as recited in claim1 wherein the image indicates the magnitude of the force placed on theretina by the membrane.
 11. A method as recited in claim 1 wherein theimage indicates a component of the force placed on the retina by themembrane.
 12. A method as recited in claim 11 wherein the component ofthe force indicated in the image is in a direction normal to thevitreo-retinal interface.
 13. An optical coherence tomography (OCT)system for generating and displaying information related to a membraneattached to the retina of an eye comprising: a light source forgenerating a beam of light; a scanner for directing the beam todifferent locations within the eye; a detector for collecting imageinformation about the reflectance distribution within the eye; aprocessor for identifying attachments of the membrane to the retina fromthe image information; and a display for displaying an image of theidentified membrane attachments.
 14. A system as recited in claim 13,wherein said image indicates the tautness of membrane.
 15. A system asrecited in claim 14, wherein the level of tautness is indicated by colorcoding.
 16. A system as recited in claim 13, wherein the image furtherindicates the disruption of tissue layers within the eye.
 17. A systemas recited in claim 13, wherein the membrane is displayed as an overlaywith respect to an en face image of the eye.
 18. A system as recited inclaim 13, wherein said image further indicates holes associated with themembrane attachments.
 19. A system as recited in claim 13, wherein saidimage includes B-scans of one or more orientations through a selectedpoint of membrane attachment.
 20. A system as recited in claim 19,wherein the orientation of the B-scan is automatically selectedaccording to the membrane and retina geometry.
 21. A system as recitedin claim 13 wherein the image indicates the magnitude of the forceplaced on the retina by the membrane.
 22. A system as recited in claim13 wherein the image indicates a component of the force placed on theretina by the membrane.
 23. A system as recited in claim 22 wherein thecomponent of the force indicated in the image is in a direction normalto the vitreo-retinal interface.